2023 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Alzheimer’s disease and a prospective hearing-related serum biomarker
Can biomarkers from the ear allow us to diagnose Alzheimer’s earlier?
Jing Zheng, Ph.D.
Northwestern University
Chicago, IL - United States
Background
Recent studies suggest brain changes associated with Alzheimer’s occur decades before clinical symptoms, such as changes in memory, thinking and reasoning, appear. Dementia researchers are working to find improved approaches of early detection of Alzheimer’s, long before onset of symptoms. Currently, researchers can detect brain changes in a living person through either a brain scan or by measuring biological markers (biomarkers) in the cerebrospinal fluid (CSF; the biological fluid surrounding the brain and spinal cord). While some advanced techniques can very accurately identify Alzheimer’s related brain changes, these can be invasive. This project aims to identify less invasive biomarkers in a part of the body that is not typically investigated in Alzheimer’s: the ear.
The brain is surrounded by CSF, which contains proteins from the brain and can be used to diagnose a number of diseases. The CSF comes in direct contact with the perilymph which is a fluid repository in the body that connects to the ear. As a result, when proteins associated with Alzheimer’s start to build up in the CSF, they can also reach the perilymph and the ear.
Outer hair cells, or OHCs, are an important cell type in the ear that are necessary for hearing. When proteins like beta-amyloid, a hallmark protein found in Alzheimer’s, reach these OHCs, they can stress them and cause the release of a protein called Ocm. Ocm normally buffers calcium that is important for the signaling that takes place during the process of hearing. But elevated levels of Ocm can actually be detected in the bloodstream, which means that through the ear, there is a potentially testable link between the brain and blood.
Research Plan
This project will examine two important questions related to this pathway : 1) is there significant amyloid reaching the OHCs to cause stress and Ocm elevation and 2) can this elevation be detected in the blood? They will use genetically-engineered Alzheimer’s like mice that produce beta-amyloid in the brain. They will then examine the inner ears of these mice to identify markers of stress caused by beta-amyloid and any cell types that may be more vulnerable to beta-amyloid. They will also examine the blood of these mice as stress on the OHCs and the ear increases to see if Ocm increases as well. Finally, they will have the mice perform basic behavioral tasks (e.g. solving a maze, recognizing new objects) to compare the increasing stress in the ear to changes in the mice’s cognitive capacity.
Impact
This study has the potential to identify new fluid biomarkers for Alzheimer’s that could be used to help diagnose patients earlier. It also has the potential to expand our understanding of how the brain and ear are connected, and identify new opportunities for further research.